Cholinergic regulation of fuel-induced hormone secretion and respiration of SUR1−/− mouse islets

Neural and endocrine factors (i.e., Ach and GLP-1) restore defective glucose-stimulated insulin release in pancreatic islets lacking sulfonylurea type 1 receptors (SUR1−/−) (Doliba NM, Qin W, Vatamaniuk MZ, Li C, Zelent D, Najafi H, Buettger CW, Collins HW, Carr RD, Magnuson MA, and Matschinsky FM. Am J Physiol Endocrinol Metab 286: E834–E843, 2004). The goal of the present study was to assess fuel-induced respiration in SUR1−/− islets and to correlate it with changes in intracellular Ca2+, insulin, and glucagon secretion. By use of a method based on O2 quenching of phosphorescence, the O2 consumption rate (OCR) of isolated islets was measured online in a perifusion system. Basal insulin release (IR) was 7–10 times higher in SUR1−/− compared with control (CON) islets, but the OCR was comparable. The effect of high glucose (16.7 mM) on IR and OCR was markedly reduced in SUR1−/− islets compared with CON. Ach (0.5 μM) in the presence of 16.7 mM glucose caused a large burst of IR in CON and SUR1−/− islets wit...